Risk Of Uterine Fibroids Research Articles

Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans

Uterine fibroids (UFs) affect 77 % of women by menopause and account for $9.4 billion in yearly healthcare costs. We recently replicated findings from the first UF genome-wide association study (GWAS), conducted in the Japanese. Here we tested these GWAS-discovered SNPs for association with UF characteristics to further assess whether risk varies by sub-phenotypes of UFs. Women were enrolled in Right from the Start (RFTS) and the BioVU DNA repository (BioVU). UF status was determined by pelvic imaging. We tested the top GWAS-associated SNPs for association with UF characteristics (RFTS: type, number, volume; BioVU: type) using covariate adjusted logistic and linear regression. We also combined association results of UF type using meta-analysis. 456 European American (EA) cases and 1,549 controls were examined. Trinucleotide repeat containing 6B (TNRC6B) rs12484776 associated with volume in RFTS (β = 0.40, 95 % CI 0.05-0.75, p = 0.024). RFTS analyses evaluating stratified quartiles of volume showed the strongest OR at rs12484776 for the largest volume (16.6-179.1 cc, odds ratio (OR) = 2.19, 95 % confidence interval (CI) 1.07-4.46, p = 0.031). Meta-analysis showed a strong association at blocked early in transport 1 homolog (BET1L) rs2280543 for intramural UFs (meta-OR = 0.51, standard error (SE) = 0.14, Q = 0.590, I = 0, p = 2.48 × 10(-6)), which is stronger than the overall association with UF risk. This study is the first to evaluate these SNPs for association with UF characteristics and suggests these genes associate with increasing UF volume and protection from intramural UF in EAs.

Vitamin d and the risk of uterine fibroids.

Uterine leiomyomata (also known as fibroids) are benign tumors of uterine smooth muscle that are characterized by overproduction of extracellular matrix. Fibroids are the leading indication for hysterectomy in the United States. The active metabolite of vitamin D has been shown to inhibit cell proliferation and extracellular matrix production in fibroid tissue culture and to reduce fibroid volume in the Eker rat. No previous study has examined whether vitamin D is related to fibroid status in women. The National Institute of Environmental Health Sciences Uterine Fibroid Study enrolled randomly selected 35- to 49-year-old women who were members of an urban health plan during 1996-1999. Fibroid status was determined by ultrasound screening of premenopausal women (620 blacks, 416 whites). Vitamin D status was assessed in stored plasma by radioimmunoassay of 25-hydroxyvitamin D (25(OH)D) and questionnaire data on sun exposure. Associations were evaluated with logistic regression, controlling for potential confounders. Only 10% of blacks and 50% of whites had levels of 25(OH)D regarded as sufficient (>20 ng/ml). Women with sufficient vitamin D had an estimated 32% lower odds of fibroids compared with those with vitamin D insufficiency (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] = 0.48-0.96). The association was similar for blacks and whites. Self-reported sun exposure ≥ 1 hour per day (weather permitting) was also associated with reduced odds of fibroids (aOR = 06. [0.4-0.9]), with no evidence of heterogeneity by ethnicity. The consistency of findings for questionnaire and biomarker data, the similar patterns seen in blacks and whites, and the biological plausibility provide evidence that sufficient vitamin D is associated with a reduced risk of uterine fibroids.

Associations between uterine fibroids and lifestyles including diet, physical activity and stress: a case-control study in China.

This study was conducted to investigate the associations between uterine fibroids and lifestyles including diet, physical activity and stress from October 2009 to April 2011 in China. This case-control study composed of 73 women with uterine fibroids and 210 women without fibroids. Uterine fibroid cases were confirmed by ultrasound diagnosis or hysterectomy surgery. Information on women's dietary habits, physical activity and stress status were collected with a validated self-administered questionnaire. A logistic regression model was used to estimate the odds ratios (OR) after controlling for age, gravidity and parity. We found that vegetable and fruit intakes and occupational intensity played positive effects on uterine fibroids. For premenopausal women, vegetable and fruit intakes (OR = 0.5; 95% CI: 0.3, 0.9) and occupational intensity (OR = 0.2; 95% CI: 0.1, 0.6) significantly decreased the risk of fibroids; conversely, BMI significantly increased the risk (OR = 1.2; 95% CI: 1.0, 1.4). However, the associations for postmenopausal women were not significant. Our findings suggested protective roles for vegetable and fruit intakes and occupational intensity on uterine fibroids, and supported the hypothesis that high BMI only increased the risk of uterine fibroids in premenopausal women.

Vitamin D3 regulates beta-catenin protein expression in human fibroid cells: implications for MED12 role in fibroid pathogenesis

Uterine fibroids are the most common benign tumors in the reproductive age women and hysterectomy is the main effective treatment for uterine fibroids till now. African American women have four times higher risk of uterine fibroids and they have ten times more hypovitaminosis D than their counterpart white women. We recently found that the mediator complex 12 (Med12) gene exon 2 somatic mutations in more than 70% cases in USA women with uterine fibroids. Med12 gene exon 2 somatic mutations are associated with uterine fibroid tumorigenicity and activation of Med12 gene regulates Wnt/beta-catenin pathways.

Serum Micronutrient Concentrations and Risk of Uterine Fibroids

Although uterine fibroids are among the most common gynecologic conditions affecting women in the United States, research on uterine fibroids is sparse. This study explored the association between micronutrients and uterine fibroids. We conducted a population-based, cross-sectional analysis of 887 women aged 20-49 who participated in the 2003-2004 National Health and Nutrition Examination Survey (NHANES). Serum micronutrient levels were collected during the health examinations, and information on uterine fibroids was assessed on self-reported questionnaires. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) while controlling for confounders. A statistically significant dose-response relationship was observed between vitamin A and uterine fibroids, after adjustment for age, race, education, body mass index (BMI), and oral contraceptive (OC) use (middle vs. low: OR 2.43, 95% CI 1.35-4.37; high vs. low: OR 2.66, 95% CI 1.16-6.10, p for trend=0.02). After adjustment, a dose-response relationship also emerged for vitamin C, although these associations were not statistically significant. It is possible that certain micronutrients affect uterine fibroid development. If this is confirmed in large prospective studies, clinicians could advise susceptible populations on dietary changes to reduce their risk of uterine fibroids.

Pesticide Exposures and Uterine Fibroid Risk Among Farming Women

Pesticide Exposures and Uterine Fibroid Risk Among Farming Women

Association of Germline Mutations in the Fumarate Hydratase Gene and Uterine Fibroids in Women With Hereditary Leiomyomatosis and Renal Cell Cancer

To investigate the risk of uterine fibroids and other reproductive risk factors in women with hereditary leiomyomatosis and renal cell cancer (HLRCC). Case-control study. National Institutes of Health, Rockville, Maryland. Patients A family-based case-control study was conducted between July 1, 2004, and June 30, 2006, including 105 women from families with HLRCC ascertained throughout North America. A telephone interview was conducted with all participants using a standardized questionnaire that elicited information about their menstrual, pregnancy, uterine fibroid, and hormonal contraceptive use history. Diagnosis of uterine fibroids was confirmed by pathologic diagnosis and by medical record review. DNA was extracted from blood samples and was screened for germline mutations in the fumarate hydratase (FH) gene. FH germline mutation status, presence of uterine fibroids, age at diagnosis, and symptoms and treatment of uterine fibroids. Of 105 women, 77 reported a history of uterine fibroids. Regardless of uterine fibroid status, 75 of 105 women had a germline mutation in FH (FH(mut) positive). The risk of uterine fibroids in FH(mut)-positive women was statistically significantly increased compared with that in FH(mut)-negative women (odds ratio [OR], 7.6; 95% confidence interval [CI], 2.9-20.0), as it was among women clinically affected with HLRCC compared with those clinically unaffected with HLRCC (8.6; 3.1-24.0). The median age at uterine fibroid diagnosis for FH(mut)-positive women (28 years) was significantly younger than that for FH(mut)-negative women (38 years) (P =.03). Women with a germline mutation in FH or clinically affected with HLRCC reported younger age at menarche (P < .004) compared with FH(mut)-negative women (P = .02) or women who were clinically unaffected with HLRCC. Women with HLRCC were more likely to have had treatment for uterine fibroids (OR, 4.6; 95% CI, 1.4-15.8), including hysterectomy (P =.02) at an earlier age compared with women who were clinically unaffected with HLRCC. This study provides the first evidence (to our knowledge) that women with germline mutations in FH and with clinical HLRCC have an increased risk of developing uterine fibroids. These women also have a younger age at uterine fibroid diagnosis and are more likely to have treatment for uterine fibroids at a younger age than women without HLRCC in their families.

Selected metabolic parameters and the risk for uterine fibroids

Objective To analyze the possible association between insulin resistance and dyslipidemia with uterine fibroids, using objective metabolic measurements. Method A cross-sectional study of 56 women with uterine fibroids (case group) and 20 women without fibroids (control group). Levels of fasting glucose, insulin, C-peptide, sex hormone-binding globulin, and the lipid panel were measured. The short insulin tolerance test was performed. Body mass index, atherogenic index, and the indicator of insulin resistance (Kitt) were also calculated. Results Women with fibroids had significantly higher levels of serum HDL-cholesterol compared with control patients (1.8 ± 0.3 vs 1.6 ± 0.5; P < 0.05). Women with fibroids aged 30–45 years had significantly lower LDL-cholesterol levels than comparative control patients (2.9 ± 0.7 vs 3.4 ± 0.9; P < 0.05). A positive correlation between volume of the largest fibroid and serum HDL-cholesterol level was found in women aged 30–45 years. There were no differences in indicators of insulin resistance between the groups. Conclusion Insulin resistance was not shown to be a risk factor for fibroids. There is a negative association between some parameters of metabolic syndrome and fibroid volume.

Lignan and isoflavone excretion in relation to uterine fibroids: a case-control study of young to middle-aged women in the United States

Uterine fibroids are hormonally responsive; estradiol and progesterone stimulate their growth, and gonadotrophin-releasing hormone agonists shrink them. Phytoestrogens, including isoflavones and lignans, can act as weak estrogens or antiestrogens. The objective of this case-control study was to evaluate the relation between uterine fibroid risk and phytoestrogen exposure. Two overnight urine collections (48 h apart) from 170 uterine fibroid cases and 173 controls were analyzed for isoflavonoids (ie, daidzein, genistein, equol, and O-desmethylangolensin) and lignans (enterodiol and enterolactone). Logistic regression was used to determine associations between the mean excretion of the 2 collections and the risk of uterine fibroids. Unadjusted isoflavone excretion did not differ significantly between cases and controls (2.33 +/- 5.82 and 2.60 +/- 5.90 nmol/mg Cr, respectively; P = 0.68), but cases excreted significantly less lignans than did controls (2.86 +/- 3.45 and 4.57 +/- 6.67 nmol/mg Cr, respectively; P < 0.01). The trend for a reduced risk of uterine fibroids with increasing quartiles of lignan excretion was significant (odds ratio for highest versus lowest quartile = 0.31; 95% CI: 0.17, 0.58; P for trend < 0.01). When adjusted for age, BMI, race, family history of uterine fibroids, and isoflavone excretion, this trend remained but was attenuated (P = 0.07). Our findings suggest a modest inverse association between lignan excretion and uterine fibroid risk. Whether this relation represents an effect of lignans per se or of other constituents of lignan-containing foods on the development of uterine fibroids remains to be determined. No association was found between isoflavone excretion and uterine fibroids; however, the intake of soy foods, the primary source of isoflavones, was low in this population.

Variation in the association of alcohol intake with uterine fibroids by race and tumor size

Purpose Uterine fibroids are prevalent benign tumors and are the leading indication for hysterectomy in the United States. Hormonal dependence for development and growth of these tumors suggests the role of estrogen-promoting factors. Alcohol intake has been associated with higher concentrations of estrogen among premenopausal women and has been implicated in other hormonally related conditions, including breast cancer. We hypothesized that alcohol intake is associated with an increased risk of uterine fibroids. Methods The study population consisted of 1146 premenopausal black or white women from the NIEHS Uterine Fibroid Study. Participants were randomly selected 35- to 49-year-old members of an urban health plan. Assessment of uterine fibroids was performed primarily through transvaginal ultrasounds. Race-stratified unconditional logistic regression was used to calculate prevalence odds ratios (OR) and 95% confidence intervals (CI) for the association of uterine fibroids with self-reported current alcohol intake and intake at age 30. Race-stratified polytomous logistic regression was used to assess these relationships with small (0.5 to Results For white women, the odds of uterine fibroids were 90% greater (95% CI = 1.0, 3.5) among those currently consuming at least 0.5 alcoholic drinks weekly compared with nondrinkers. The odds ratio with current drinking was strongest for small fibroids (OR = 4.3; 95% CI = 1.4, 12.9), and alcohol intake at age 30 was most strongly related to large tumors (OR = 1.5; 95% CI = 0.6, 3.7). There was no association of alcohol intake with uterine fibroids for black women (OR = 1.0; 95% CI = 0.7, 1.6), but the patterns for current and past drinking with fibroid size were generally similar to those for white women. Conclusion This study suggests the involvement of alcohol intake in the initiation or early growth of uterine fibroids.

Genetic culprit: Mutation increases risk for uterine fibroids

Science NewsVolume 161, Issue 10 p. 149-149 This Week Genetic culprit: Mutation increases risk for uterine fibroids Nathan Seppa, Nathan SeppaSearch for more papers by this author Nathan Seppa, Nathan SeppaSearch for more papers by this author First published: 01 July 2009 https://doi.org/10.2307/4013241AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume161, Issue109 March 2002Pages 149-149 RelatedInformation

Use of oral contraceptives and uterine fibroids: results from a case-control study.

To analyse the association between oral contraceptive use and the risk of uterine fibroids. We considered data collected in a case-control study on risk factors for uterine fibroids. We studied 843 women with uterine fibroids, whose clinical diagnosis dated back no more than two years. Controls were 1557 non-hysterectomised patients younger than 55 years admitted for acute, non-gynecological, non-hormonal, non-neoplastic conditions. A total of 254 cases (30.1%) and 360 controls (23.1%) reported ever using oral contraceptives: the odds ratio (OR) for ever vs never users was 1.1 (95% CI 0.8-1.3). The risk in current users was below unity when compared with never users (OR 0.3, 95% CI 0.2-0.6), while ex-users had a risk of fibroids comparable with never users (OR 1.1, 95% CI 0.9-1.4). The risk of uterine fibroids decreased with duration of oral contraceptive use: compared with never users, the estimated OR was 0.8 (95% CI 0.5-1.2) in ever users for four to six years and 0.5 (95% CI 0.3-0.9) for seven years or more (chi2 trend = 4.6, P = 0.03). Although the role of selection bias should be carefully evaluated, the present data suggest that uterine fibroids should not be considered a contra-indication for oral contraceptive use.

Reproductive factors and risk of uterine fibroids.

We analyzed the relation between reproductive history and risk of uterine fibroids using data from a case-control study. Cases were 621 women with histologically confirmed diagnosis of uterine fibroids. Controls were 1,051 non-hysterectomized patients. Compared with nulliparae, parous women had a relative risk (RR) of fibroids of 0.5 [95% confidence interval (CI) = 0.4-0.6], and the risk declined with number of births. The risk of fibroids also decreased with number of induced abortions (RR = 0.8 and 0.6 for women reporting one or two or more abortions, respectively). A total of 24 cases (3.9%) and 19 controls (1.8%) reported a history of infertility (RR = 2.0; 95% CI = 1.1-3.7).

Oral Contraceptive Use and Risk of Uterine Fibroids

The association between oral contraceptive (OC) use and the risk of uterine fibroids was analyzed in a case-control study conducted between 1986-1990. The subjects were 390 patients under 55 years of age with histologically confirmed fibroids and 1136 controls in hospitals for a spectrum of acute conditions (other than gynecologic, hormonal, or neoplastic) apparently unrelated to OC use. A total of 78 cases (20%) and 200 controls (18%) reported OC use. Compared with never-users, the multivariate relative risk for ever-users was 1.1 (95% confidence interval [CI] 0.8-1.5). No direct relationship emerged with duration of use, the estimated relative risk being 1.3 (95% CI 0.9-2.0) in users of OCs for less than 3 years and 0.8 (95% CI 0.5-1.3) in users for 3 years or more. The risk of fibroids was apparently (though not significantly) greater with longer recency of use: The estimated relative risks were 0.9 and 1.5, respectively, in women reporting last OC use less than 10 years before and 10 or more years before diagnosis of the disease. No relationship emerged with latency of use. There was no noteworthy interaction regarding risk of fibroids between OC use and potential covariates. These findings suggest that fibroids are unrelated to the use of OCs.

The antiestrogenic effect of cigarette smoking in women

Epidemiologic results indicate that women who smoke cigarettes are relatively estrogen-deficient. Smokers have an early natural menopause, a lowered risk of cancer of the endometrium, and an increased risk of some osteoporotic fractures. Moreover, women who smoke may have a reduced risk of uterine fibroids, endometriosis, hyperemesis gravidarum, and benign breast disease. Several possible mechanisms for these effects have been identified. Smoking does not appear to be clearly related to estradiol levels, at least in postmenopausal women, although levels of adrenal androgens are increased. Moreover, smoking appears to alter the metabolism of estradiol, leading to enhanced formation of the inactive catechol estrogens.

Epidemiologic characteristics of women with uterine fibroids: a case-control study.

Risk factors for uterine fibroids were analyzed in a hospital-based case-control study conducted in the greater Milan area, based on 275 women with histologically confirmed fibroids and 722 controls with acute nongynecologic or hormone-related conditions. Questions were asked about menstrual and reproductive characteristics, education, history of various diseases, and lifetime use of oral contraceptives and other hormonal treatments. The risk of uterine fibroids was reduced in parous women relative to nulliparous ones (relative risk 0.6) and in those who were postmenopausal (relative risk 0.1 compared with premenopausal women of the same age). Women with fibroids tended to have an earlier age at menarche and at the last birth, to be more educated, and to use intrauterine devices and oral contraceptives more frequently, although these findings were not statistically significant. Current smoking (but not past smoking) lowered the fibroid risk by about 40%. No associations were found with body mass index, history of spontaneous or induced abortions, and age at first birth.